DESCRIPTION This proposal builds on observations made during the current grant period that the over-expression of the neuronal intermediate filament protein alpha-internexin causes the formation of axonal swellings in transgenic mice, as well as observations made with GFP-intermediate filament protein chimeras which suggest an interaction between intermediate filaments and the microtubule cytoskeleton. It also builds on the recent characterization of BPAG1, which has both an intermediate filament-binding domain and an actin-binding domain. The emphasis of the current proposal is to examine proteins which interact with neuronal intermediate filaments, to identify motor proteins involved in the transport of neuronal intermediate filaments, and to make further progress in understanding the function and regulation of the neuronal intermediate filament protein a-internexin. The specific aims of this study are: (1) to study how members of the plakin family interact with neuronal intermediate filaments; (2) to study the mechanism of the transport of neuronal intermediate filaments in the axon; and (3) to continue studies on the function of alpha-internexin by generating a knockout mouse model and characterizing the resulting phenotype.